Not All Missed Doses Are the Same: Sustained NNRTI Treatment Interruptions Predict HIV Rebound at Low-to-Moderate Adherence Levels

Abstract

BackgroundWhile the relationship between average adherence to HIV potent antiretroviral therapy is well defined, the relationship between patterns of adherence within adherence strata has not been investigated. We examined medication event monitoring system (MEMS) defined adherence patterns and their relation to subsequent virologic rebound.Methods and ResultsWe selected subjects with at least 3-months of previous virologic suppression on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen from two prospective cohorts in France and North America. We assessed the risk of virologic rebound, defined as HIV RNA of >400 copies/mL according to several MEMS adherence measurements.Seventy two subjects were studied, five of them experienced virologic rebound. Subjects with and without virologic rebound had similar baseline characteristics including treatment durations, regimen (efavirenz vs nevirapine), and dosing schedule. Each 10% increase in average adherence decreased the risk of virologic rebound (OR = 0.56; 95% confidence interval (CI) [0.37, 0.81], P<0.002). Each additional consecutive day off therapy for the longest treatment interruption (OR = 1.34; 95%CI [1.15, 1.68], P<0.0001) and each additional treatment interruption for more than 2 days (OR = 1.38; 95%CI [1.13, 1.77], P<0.002) increased the risk of virologic rebound. In those with low-to-moderate adherence (i.e. <80%), treatment interruption duration (16.2 days versus 6.1 days in the control group, P<0.02), but not average adherence (53.1% vs 55.9%, respectively, P = 0.65) was significantly associated with virologic rebound.ConclusionsSustained treatment interruption may pose a greater risk of virologic rebound on NNRTI therapy than the same number of interspersed missed doses at low-to-moderate adherence.

Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications

“…The finding that food insecurity is associated with lower levels of adherence is especially important given that lower ranges of adherence are more likely to be associated with incomplete viral suppression with currently available regimens. 34 However, our data, like that of others, suggest that the association between food insecurity and viral suppression is not explained by a difference in adherence, in this case, an average yearly adherence. 14 Veterans in this study received 98% of their medications from a VA pharmacy, making our use of administrative pharmacy data one of the best available adherence measurement strategies; however, these data may not capture patterns of adherence including treatment interruptions, that may be associated with viral rebound.…”

“…14 Veterans in this study received 98% of their medications from a VA pharmacy, making our use of administrative pharmacy data one of the best available adherence measurement strategies; however, these data may not capture patterns of adherence including treatment interruptions, that may be associated with viral rebound. 34 Food insecurity was also associated with lower body mass index. However, when BMI was truncated into clinically meaningful categories, the association was marginally statistically significant.…”

Intentional Non-Adherence to Medications among HIV Positive Alcohol Drinkers: Prospective Study of Interactive Toxicity Beliefs

“…Optimal health benefits for people receiving ART depend closely on treatment adherence, with all ART regimens requiring at least 85 % adherence. 1,2 Among the known impediments to medication adherence is alcohol use. 3 Studies demonstrate that individuals who take ART and drink alcohol experience more missed doses, medication lapses, and HIV treatment failure.…”

The Importance of Social Ties in Sustaining Medication Adherence in Resource-Limited Settings

“…Third, depending on the pharmacokinetic properties of the specific medication under consideration, a high degree of punctuality in average dose-taking execution can still result in poor outcomes if the rare episodes of non-persistence (described variously as drug holidays, 9 treatment interruptions, 24 or non-permissible gaps 10 ) are sequentially concentrated in time. 24,25 Comparing the findings of Bowry et al 12 to those of DiMatteo 11 might lead one to conclude that dose-taking execution of cardiovascular medication regimens is worse among patients living in emerging and developing economies, and that the primary barriers they face are cognitive in nature. This is notably different from what has been reported in the HIV literature.…”